Project Summary/Abstract One concern about e-cigarettes is their abuse potential; however, we know of no systematic study of this in a young adult population. Abuse-liability assessments traditionally include the analysis of positive subjective effects and of self-administration, but these may fall short of accurately characterizing the abuse potential of tobacco products because recent preclinical studies indicate some of nicotine's abuse liability is due to the ability of nicotine to enhance the rewarding effects of non-drug reinforcers. However, only recently have reports of reinforcement enhancement emerged with human adult tobacco smokers. Furthermore, recent data from our rodent laboratory has demonstrated that a secondary consequence of reinforcement enhancement by nicotine is reinforcer devaluation; when non-pharmacological reinforcers are experienced in the presence of nicotine, and then in the absence of nicotine, their reinforcing value diminishes well-below their pre-nicotine exposure levels. Our rodent data suggest that reinforcer devaluation is not related to physical symptoms of withdrawal. If these results can be applied to human use of nicotine, they would suggest that in order for the world of natural reinforcers to retain their motivational value, they need to be experienced in the continual presence of nicotine. Therefore, reinforcement (a) enhancement and (b) devaluation may work in unison to escalate use of nicotine-containing products. Most importantly, our data suggest reinforcement enhancement and devaluation can occur prior to the onset of physical dependence associated with daily smoking. Thus, these two processes may be especially important in the young adult population, which is the age period during which the transition from occasional-to- habitual tobacco/nicotine use occurs. Reinforcement enhancement and devaluation will be evaluated in the proposed experiment by exposing a young-adult population of tobacco experimenters to e-cigarettes. These young adults will self-administer one of three doses of nicotine (0, 6, or 12 mg/ml) during several laboratory sessions. Changes in reinforcer efficacy resulting from nicotine exposure will be evaluated by testing changes in video-game behavior. Video games are an ecologically valid and potent reinforcer for this particular population, and we believe video gaming may be particularly sensitive to nicotine's reinforcing- enhancing effects. Furthermore, to examine whether nicotine delivered by e-cigarettes produces some of the psychological effects that are characteristic of tobacco cigarettes, changes in (i) general hedonic pleasure, (ii) cognitive performance, and (iii) nicotine withdrawal will be assessed during the laboratory sessions. Data from this battery of psychological tests may provide information on whether these variables (i-iii) moderate or mediate changes in reinforcer efficacy.